A highly active polymer, a biochip, and a preparation method and application thereof

Abstract

The present application relates to the field of biochip technology, and specifically to a highly active polymer, a biochip, and a preparation method and application thereof. The preparation method of the highly active polymer comprises: preparing pentafluorophenol acrylate with acrylic acid and pentafluorophenol; polymerizing pentafluorophenol acrylate under the action of an initiator to obtain polypentafluorophenol acrylate; subjecting polypentafluorophenol acrylate to an amidation reaction with compound A and compound B to obtain a highly active polymer; wherein compound A contains an azide group and an amino functional group, and compound B contains at least one of an amino group, a carboxyl group, an epoxy group or a cyano functional group. The present application prepares polypentafluorophenol acrylate by homopolymerizing pentafluorophenol acrylate, using polypentafluorophenol acrylate as a polymer platform, and introducing the functional group into the polymer structure through an amidation reaction with organic matter containing different functional groups. The synthesis process is simple and the preparation cost is low.

Description

Technical Field

[0001] The present application relates to the field of biochip technology, and in particular to a highly active polymer, a biochip, and a preparation method and application thereof. Background Art

[0002] With the rapid development of biotechnology, high-throughput, fast, and low-cost biochip technology has become the focus of research and development, among which the construction of biochips is particularly important. At present, biochips are mainly prepared by surface modification technology and polymer-coated substrates. They have good biocompatibility, low nonspecific adsorption, high reactivity, high reactivity density, high wettability and other physical and chemical properties, thus providing a good carrier for the subsequent sequencing process, so as to facilitate subsequent PCR and fluorescence detection.

[0003] At present, polymers for biochips are prepared by copolymerizing monomers with different structures. For example, patent application CN115010852A prepares polymers for surface modification of sequencing chips by copolymerizing three unsaturated organic substances containing different functional groups; patent CN114573764B prepares polymers for chips by copolymerizing two unsaturated organic substances containing different functional groups.

[0004] However, the preparation of polymers through copolymerization requires more monomer molecules, which has high preparation costs and complex synthesis processes. In addition, the uniformity and functional group distribution of copolymers are difficult to control, resulting in defects such as low probe density, high nonspecific adsorption, and low signal-to-noise ratio in biochips, which limits the development of the biochip field. Summary of the invention

[0005] The present application provides a highly active polymer, a biochip, and a preparation method and application thereof, aiming to solve the problems of high preparation cost and complex synthesis process of existing copolymers for biochips, as well as poor uniformity and uneven functional group distribution of the copolymers.

[0006] In order to achieve the above objectives, the present application adopts the following technical solutions.

[0007] In a first aspect of the present application, a method for preparing a highly active polymer is provided, comprising:

[0008] Preparation of pentafluorophenol acrylate from acrylic acid and pentafluorophenol;

[0009] Pentafluorophenol acrylate is polymerized under the action of an initiator to obtain polypentafluorophenol acrylate;

[0010] The poly(pentafluorophenol) acrylate undergoes an amidation reaction with compound A and compound B to obtain a highly active polymer;

[0011] Wherein, the compound A contains azide and amino functional groups, and the compound B contains at least one of amino, carboxyl, epoxy or cyano functional groups.

[0012] In some embodiments, the structural formula of compound A is:

[0013]

[0014] Wherein, x is an integer from 1 to 30;

[0015] In some embodiments, the structural formula of compound B is:

[0016]

[0017] Among them, R is one of NH2-CH2-, NH2-CHCH3-, and NH2-C(CH3)2-.

[0018] In some embodiments, the sum of the moles of the compound A and the compound B is equal to the mole of the polypentafluorophenol acrylate.

[0019] In some embodiments, the molar ratio of compound A to compound B is (0.19-1):1.

[0020] In some embodiments, the molar ratio of the pentafluorophenol acrylate monomer to the initiator is (5000-30000):1, and the initiator is azobisisobutyronitrile, azobisisoheptanenitrile or potassium persulfate;

[0021] and / or:

[0022] The polymerization temperature is 30-85°C;

[0023] and / or:

[0024] The temperature of the amidation reaction is 20-60°C.

[0025] In a second aspect of the present application, a highly active polymer prepared by the above preparation method is provided.

[0026] In a third aspect of the present application, a biochip is provided, comprising a chip substrate, and a polymer grafted onto the surface of the chip substrate;

[0027] The polymer is a highly active polymer prepared by the above preparation method.

[0028] In some embodiments, the chip substrate is modified with active groups;

[0029] The active group is at least one of an amino group, an epoxy group, an alkynyl group, an alkenyl group, an isothiocyanate group or a carboxyl group.

[0030] In some embodiments, the biochip further comprises a biological component, and the biological component is grafted to the highly active polymer.

[0031] Compared with the prior art, the beneficial effects of this application are:

[0032] The present invention prepares polypentafluorophenol acrylate by homopolymerizing pentafluorophenol acrylate, uses polypentafluorophenol acrylate as a polymer platform, and introduces functional groups into the polymer structure through amidation reaction with organic substances containing different functional groups. The synthesis process is simple and the preparation cost is low.

[0033] The molecular weight of the polymer prepared in the present application is controllable and has good uniformity; the distribution of the functional groups is uniform and the distribution density is adjustable. The biochip using the high-activity polymer of the present application has good compatibility, high reactivity, low nonspecific adsorption, high wettability, and high signal-to-noise ratio. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments recorded in the present application, and for ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0035] Figure 1 The gel permeation chromatogram (GPC) of the polypentafluorophenol acrylate prepared in Example 1;

[0036] Figure 2 This is the NMR test spectrum of polypentafluorophenol acrylate prepared in Example 1;

[0037] Figure 3 This is the NMR test spectrum of the highly active polymer prepared in Example 1;

[0038] Figure 4 This is the NMR test spectrum of the highly active polymer prepared in Example 2;

[0039] Figure 5 The gel permeation chromatograms of the polypentafluorophenol acrylate prepared in Example 1 and Examples 3-5;

[0040] Figure 6 The gene sequencing data diagram of the biochip containing the polymers of Example 1 and Comparative Example 1. DETAILED DESCRIPTION

[0041] The technical solutions in the embodiments of the present application will be described clearly and completely below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, rather than all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0042] In the following description of this embodiment, the terms "include", "comprising", "having" and "containing" are all open terms, meaning including but not limited to.

[0043] In the following description of this embodiment, the term "and / or" is used to describe the association relationship of associated objects, indicating that there may be three relationships. For example, A and / or B can represent: A exists alone, B exists alone, and A and B exist at the same time. A and B can be singular or plural. The character " / " generally indicates that the associated objects before and after are in an "or" relationship.

[0044] In the following description of this embodiment, the term "at least one" refers to one or more, and "plurality" refers to two or more. "At least one of the following" or similar expressions refers to any combination of these items, including any combination of single items or plural items. For example, "at least one of a, b or c", or "at least one of a, b and c", can all represent: a, b, c, ab (i.e., a and b), ac, bc, or abc, where a, b, c can be single or multiple, respectively.

[0045] The terms used in the embodiments of the present application are only for the purpose of describing specific embodiments, and are not intended to limit the present application. The singular forms "a", "an" and "the" used in the embodiments of the present application and the appended claims are also intended to include plural forms, unless the context clearly indicates other meanings.

[0046] Those skilled in the art should understand that in the following description of the embodiments of the present application, the order of serial numbers does not mean the order of execution, some or all of the steps can be executed in parallel or sequentially, and the execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0047] Those skilled in the art will appreciate that the numerical ranges in the embodiments of the present application are to be understood as each intermediate value between the upper and lower limits of the scope also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present application. The upper and lower limits of these smaller ranges may be independently included or excluded in the scope.

[0048] Unless otherwise specified, the technical / scientific terms used herein have the same meanings as those generally understood by those skilled in the art to which this application belongs. Although this application only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of this application. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0049] In a first aspect, the present application provides a method for preparing a highly active polymer, comprising:

[0050] Pentafluorophenol acrylate is prepared from acrylic acid and pentafluorophenol, and the reaction formula is:

[0051]

[0052] Pentafluorophenol acrylate is polymerized under the action of an initiator to obtain polypentafluorophenol acrylate, and the reaction formula is:

[0053]

[0054] The poly(pentafluorophenol) acrylate undergoes an amidation reaction with compound A and compound B to obtain a highly active polymer;

[0055] Wherein, the compound A contains an azide group and an amino functional group, and the compound B contains any one of an amino group, a carboxyl group, an epoxy group or a cyano functional group.

[0056] In the present application, pentafluorophenol acrylate is homopolymerized to obtain polypentafluorophenol acrylate, wherein the molecular weight of the polymerized product polypentafluorophenol acrylate can be adjusted by adjusting the ratio of the monomer and the initiator. Polypentafluorophenol acrylate is used as a polymer platform to undergo amidation reaction with compound A and compound B containing different functional groups, thereby introducing functional groups into the polymer molecule.

[0057] In the present application, compound A contains an azide group and an amino functional group. Preferably, one end of the molecular structure of compound A is an azide group, and the other end is an amino group. Specifically, compound A can be selected from compounds having the following structure:

[0058]

[0059] Wherein, x is an integer from 1 to 30;

[0060] Compound B contains at least one of an amino group, a carboxyl group, an epoxy group or a cyano group. Preferably, compound B contains an amino group and a hydroxyl group, or an amino group and an amide group. Specifically, compound B can be selected from compounds having the following structure:

[0061]

[0062] Among them, R is one of NH2-CH2-, NH2-CHCH3-, and NH2-C(CH3)2-.

[0063] In the present application, the preparation of pentafluorophenol acrylate from acrylic acid and pentafluorophenol adopts the existing conventional technology, or uses the existing commercial pentafluorophenol acrylate.

[0064] In the present application, pentafluorophenol acrylate monomer is polymerized under the action of an initiator, wherein the polymerization temperature is 30-85°C, and the initiator is selected from azobisisobutyronitrile, azobisisoheptanenitrile or potassium persulfate; preferably, the molar ratio of pentafluorophenol acrylate monomer to initiator is (5000-30000): 1. Under the temperature and molar ratio conditions, the structure of polypentafluorophenol acrylate is uniform, and its molecular weight is 14000-134000, and the molecular weight can be adjusted within the molecular weight range according to actual requirements.

[0065] Pentafluorophenol polyacrylate is subjected to amidation reaction with compound A and compound B at 20-60° C. Preferably, the sum of the molar numbers of compound A and compound B is equal to the molar number of pentafluorophenol polyacrylate, so that the pentafluorophenol groups in the polymer are completely replaced and the functional groups are evenly distributed; more preferably, the molar ratio of compound A to compound B is (0.19-1):1, and the distribution density of the functional groups is adjusted within the molar ratio range. The biochip prepared with the obtained high-activity polymer has good compatibility, high reactivity, low nonspecific adsorption and high wettability.

[0066] In the second aspect, the present application provides a highly active polymer prepared by the above preparation method. The highly active polymer has controllable molecular weight and good uniformity; the functional groups are evenly distributed and the distribution density is adjustable, and is suitable for preparing biochips.

[0067] In a third aspect, the present application provides a biochip, comprising a chip substrate, and a polymer grafted onto the surface of the chip substrate; the polymer is a highly active polymer prepared by the above-mentioned preparation method.

[0068] The chip substrate is modified with active groups, including at least one of amino, epoxy, alkynyl, alkenyl, isothiocyanate or carboxyl groups; the chip substrate is selected from one of ultra-white glass, silicon wafer, organic glass, cellulose, COC organic matter and the like.

[0069] After cleaning the chip substrate, the silane coupling agent is vaporized by chemical vapor deposition and evenly dispersed on the surface of the chip substrate. The silane coupling agent is used to modify the active group of the chip substrate. In the present application, the silane coupling agent is selected from at least one of 3-aminopropyltriethoxysilane, 3-(2,3-epoxypropoxy)propyltrimethoxysilane, 3-(triethoxysilyl)propyl)ethyl-1,2-diamine, 3-(dimethoxy(methyl)silyl)propyl)ethyl-1,2-diamine, trimethylpropargylsilane, and prop-2-yn-1-yl(3-(triethoxysilyl)propyl)carbamate.

[0070] The active groups in the silane coupling agent deposited on the surface of the chip substrate, such as amino, epoxy, alkynyl, alkenyl, isothiocyanate or carboxyl, undergo click chemical reaction with the azide groups in the highly active polymer to graft the highly active polymer onto the surface of the chip substrate; then the biological component is grafted and connected with the highly active polymer to obtain a biochip. Among them, the biological component can be selected from proteins, nucleic acids, polysaccharides or cells. The biochip using the highly active polymer of the present application has good compatibility, high reactivity, low nonspecific adsorption, high wettability, and high signal-to-noise ratio.

[0071] The present application is further described below by way of examples.

[0072] Example 1

[0073] This embodiment provides a method for preparing a highly active polymer, comprising:

[0074] Step 1. Synthesis of pentafluorophenol acrylate monomer

[0075] 10 g of acrylic acid and 3.557 g of pentafluorophenol were added to a round-bottom flask, 71 mL of anhydrous dichloromethane was added, and ultrasonic mixing was performed uniformly. Then 11.36 g of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCL) was added, and mixed uniformly. Nitrogen was passed through for 10 min to remove oxygen, and the mixture was sealed and reacted at 25 ° C for 4 h. The degree of reaction was detected by TLC thin-layer chromatography. After the reaction was complete, petroleum ether was used as the eluent, and the organic phase was purified by a silica column, and finally vacuum dried to obtain pentafluorophenol acrylate.

[0076] Step 2. Synthesis of polypentafluorophenol acrylate

[0077] Azobisisobutyronitrile was dissolved in tetrahydrofuran to prepare an initiator solution with a concentration of 1 mg / mL; 0.7 g of pentafluorophenol acrylate was added to a Schlenk bottle, and 34.5 μL of azobisisobutyronitrile solution was added to make the molar ratio of pentafluorophenol acrylate to the initiator 14000:1; then 982.75 μL of tetrahydrofuran was added, and then nitrogen was passed through the reaction solution for 10 minutes to remove oxygen, and the Schlenk bottle was sealed and placed in a 70°C oil bath to react overnight. Then the reaction solution was precipitated with ice methanol twice and vacuum dried to obtain polypentafluorophenol acrylate.

[0078] The molecular weight of the prepared poly(pentafluorophenol acrylate) was determined by GPC, and the weight average molecular weight was 81,000. Figure 1 The prepared poly(pentafluorophenol acrylate) was subjected to nuclear magnetic resonance testing, and its NMR graph is shown in Figure 2 As shown, Figure 2 The left picture in the middle is the H spectrum, and the right picture is the F spectrum.

[0079] from Figure 2 It can be seen that the chemical shifts of 3.08ppm and 2.66-1.80ppm are the chemical shifts of H of CH and CH2 on the main chain, respectively, and the integrated areas are approximately equal to 1:2; the chemical shifts at -152ppm, -156ppm, and -162ppm are the chemical shifts of F on PFP, and the integrated areas are 2:1:2, respectively. Through NMR analysis, it was found that poly(pentafluorophenol) acrylate was successfully synthesized.

[0080] Step 3. Synthesis of highly active polymers

[0081] 100 mg of poly(pentafluorophenol acrylate) was added into a round-bottom flask, and 1 ml of tetrahydrofuran was added, and the mixture was stirred evenly. Then, 0.2 mL of N,N-diisopropylethylamine was added, and the solution pH was measured to be >10. Then, compound A and compound B were added in a molar ratio of 1:5, and the mixture was placed in an oil bath at 25°C to react for 2 h. The product was then precipitated with methanol, and the reaction was repeated twice. Finally, the mixture was dried under vacuum to obtain a highly active polymer, which was recorded as product 1.

[0082] The reaction formula is as follows:

[0083]

[0084] Wherein, m and n are positive integers.

[0085] The product 1 prepared in Example 1 was subjected to nuclear magnetic resonance testing, and its NMR graph is as follows: Figure 3 As shown. Figure 3It can be seen that the peak near 2.48ppm is the peak of 2 H on compound B, and the peak near 4.0ppm is the peak of 2 H on compound A. By integrating the peak areas, it can be obtained that m:n≈1:5, which is equivalent to the feed ratio. The existence of characteristic peaks proves the successful synthesis of highly active polymers.

[0086] Example 2

[0087] This embodiment provides a method for preparing a highly active polymer, comprising:

[0088] Step 1 and step 2 of Example 2 are the same as those of Example 1;

[0089] Step 3, add 50 mg of poly(pentafluorophenol)acrylate to a round-bottom flask, add 2 mL of a mixed solution of tetrahydrofuran / N,N-dimethylformamide, stir evenly, then add 0.2 mL of N,N-diisopropylethylamine, measure the solution pH>10, then add compound A and compound B in a molar ratio of 1:5, place at 25°C room temperature to react overnight, and rotate at 500 rpm. Then use methanol to precipitate the product, and finally vacuum dry to obtain a highly active polymer, which is recorded as product 2.

[0090] The reaction formula is as follows:

[0091]

[0092] Wherein, m and n are positive integers.

[0093] The product 2 prepared in Example 2 was subjected to nuclear magnetic resonance testing, and its NMR graph is as follows: Figure 4 As shown, Figure 4 The left side is the H spectrum, Figure 4 The right side is the F spectrum. Figure 4 It can be seen that the NMR peak of product 2 is correct, and the actual m:n is approximately equal to 1:5. The F spectrum also confirms that there is almost no PFP residue on the main chain, proving the successful synthesis of a highly active polymer.

[0094] Example 3

[0095] This embodiment provides a method for preparing a highly active polymer, comprising:

[0096] The difference between Example 3 and Example 1 is that in step 2, the molar ratio of the monomer to the initiator is 5000:1, and the rest is the same as Example 1. The molecular weight of the prepared polypentafluorophenol acrylate was measured by GPC, and the weight average molecular weight was 14582.

[0097] Example 4

[0098] This embodiment provides a method for preparing a highly active polymer, comprising:

[0099] The difference between Example 4 and Example 1 is that in step 2, the molar ratio of the monomer to the initiator is 10000:1, and the rest is the same as Example 1. The molecular weight of the prepared polypentafluorophenol acrylate was measured by GPC, and the weight average molecular weight was 69929.

[0100] Example 5

[0101] This embodiment provides a method for preparing a highly active polymer, comprising:

[0102] The difference between Example 5 and Example 1 is that in step 2, the molar ratio of the monomer to the initiator is 28000:1, and the rest is the same as that of Example 1. The molecular weight of the prepared polypentafluorophenol acrylate was measured by GPC, and the weight average molecular weight was 134000.

[0103] The molecular weight of the polypentafluorophenol acrylate prepared in Examples 1 and 3-5 was measured. The results are as follows: Figure 5 As shown. Figure 5 It can be seen that when the molar ratio of pentafluorophenol acrylate monomer to initiator is in the range of (5000-30000):1, the molecular weight of the prepared polypentafluorophenol acrylate is 14000-134000, and the molecular weight can be adjusted within this molecular weight range according to actual requirements.

[0104] Example 6

[0105] The highly active polymer prepared in Example 1 was used to prepare a biochip, and the preparation method was as follows:

[0106] The glass substrate was ultrasonically cleaned at 45°C for 15 min using anhydrous ethanol, 1M NaOH solution, and deionized water, respectively. After cleaning, the glass substrate was blown dry with nitrogen, and then placed in a chemical vapor deposition instrument and treated with oxygen plasma for 10 min; then the glass substrate was placed in a vacuum drying oven, evacuated to a pressure below 10 bar, and then replaced with nitrogen 3 times. 50 μL of prop-2-yn-1-yl (3-(triethoxysilyl)propyl) carbamate was placed in a vacuum oven, the door was quickly closed, and the pressure was evacuated to a pressure below 1 bar. The oven temperature was set to 72°C and kept constant for 4 hours, then the temperature was set to 130°C and kept constant for 3.3 hours, and then cooled to room temperature to obtain a glass substrate modified with active groups.

[0107] The high-performance polymer prepared in Example 1 was used to prepare a solution with a concentration of 1 mg / mL, and the glass substrates modified with active groups were immersed in the solution, respectively, and reacted in an oven at 60° C. for 1.5 h to graft the polymer onto the surface of the glass substrate, which was recorded as substrate 1;

[0108] 10 μM DBCO-space18-A30 was dissolved in sodium citrate buffer solution to prepare a solution; substrate 1 was placed in the solution and reacted overnight at 38° C. After the reaction, the surface of the glass substrate was cleaned with sodium citrate buffer solution to obtain a biochip modified with a nucleic acid sequence, which was recorded as biochip 1.

[0109] Comparative Example 1

[0110] The existing commercial biochip polymer has the following structural formula:

[0111]

[0112] Comparative Example 2

[0113] The highly active polymer of Comparative Example 1 was used to prepare a biochip.

[0114] The difference between Comparative Example 2 and Example 6 is that the highly active polymer prepared in Example 1 in Example 6 is replaced by the highly active polymer in Comparative Example 1, and the rest is the same as Example 6. The biochip prepared in Comparative Example 2 is recorded as Biochip 2.

[0115] Biochip 1 and Biochip 2 were sequenced using a Salus Pro commercial sequencer, and the second-generation sequencing method, i.e., "sequencing by synthesis", was used for gene sequencing. The results are shown in the figure. Figure 6 shown. Figure 6 The left side shows the test results of biochip 1, and the right side shows the test results of biochip 2. Figure 6 It can be seen from the data that the key indicators of the biochip 1 made of the high-activity polymer prepared in the present application all meet the standards, and its effect is better than the biochip 2 made of commercial polymer.

[0116] Although the present application has been described in detail in general terms and in specific embodiments in this specification, it is obvious to those skilled in the art that some modifications or improvements may be made to the present application. Therefore, these modifications or improvements made without departing from the spirit of the present application are within the scope of protection claimed in the present application.

Claims

1. A method for preparing a highly active polymer, characterized in that: include: Preparation of pentafluorophenol acrylate from acrylic acid and pentafluorophenol; Pentafluorophenol acrylate is polymerized under the action of an initiator to obtain polypentafluorophenol acrylate; The poly(pentafluorophenol) acrylate undergoes an amidation reaction with compound A and compound B to obtain a highly active polymer; Wherein, the compound A contains an azido group and an amino functional group, and its structural formula is: ； or ； Wherein, x is an integer from 1 to 30; The compound B contains an amino group, and any one of a hydroxyl group, an amide group or a carboxyl group.

2. The method for preparing a highly active polymer according to claim 1, characterized in that: The structural formula of the compound B is: 、 、 、R-COOH; Among them, R is one of NH2-CH2-, NH2-CHCH3-, and NH2-C(CH3)2-.

3. The method for preparing a highly active polymer according to claim 1, characterized in that: The sum of the moles of the compound A and the compound B is equal to the mole of the polypentafluorophenol acrylate.

4. The method for preparing a highly active polymer according to claim 3, characterized in that: The molar ratio of compound A to compound B is (0.19-1):

1.

5. The method for preparing a highly active polymer according to claim 1, characterized in that: The initiator is azobisisobutyronitrile, azobisisoheptylnitrile or potassium persulfate; the molar ratio of the pentafluorophenol acrylate monomer to the initiator is (5000-30000):1; and / or: The polymerization temperature is 30-85°C; and / or: The temperature of the amidation reaction is 20-60°C.

6. A highly active polymer prepared by the preparation method according to any one of claims 1 to 5.

7. A biochip, characterized in that: It includes a chip substrate, and a polymer grafted onto the surface of the chip substrate; The polymer is a highly active polymer prepared by the preparation method according to any one of claims 1 to 5.

8. The biochip according to claim 7, characterized in that: The chip substrate is modified with active groups; The active group is at least one of an amino group, an epoxy group, an alkynyl group, an alkenyl group, an isothiocyanate group or a carboxyl group.

9. The biochip according to claim 7 or 8, characterized in that: The biochip further comprises a biological component, and the biological component is grafted with the highly active polymer.

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